4.7 HIV Diagnosis, Antiretroviral Therapy & Prevention

Management of Human Immunodeficiency Virus (HIV), sexually transmitted infections (STIs), and opportunistic infections (OIs) is among the most frequently tested areas on the ABIM examination. This section provides detailed guidance on diagnostic algorithms, antiretroviral therapy (ART) selection, pre/post-exposure prophylaxis, CD4-stratified opportunistic infections, and syphilis staging.

1. HIV Diagnosis & Initial Evaluation

CDC Diagnostic Testing Algorithm

• Step 1: 4th-Generation HIV-1/2 Antigen/Antibody Combination Immunoassay: Detects both HIV-1 and HIV-2 antibodies and the HIV-1 p24 antigen (detectable within 14–20 days after infection, significantly narrowing the diagnostic window compared to antibody-only assays).
  • If non-reactive -> Negative for HIV infection.
  • If reactive -> Proceed to Step 2.
• Step 2: HIV-1 / HIV-2 Antibody Differentiation Immunoassay:
  • If positive for HIV-1 or HIV-2 antibodies -> Confirmed HIV-1 or HIV-2 infection.
  • If negative or indeterminate (antibodies not yet formed in acute early infection) -> Proceed to Step 3.
• Step 3: HIV-1 RNA Qualitative / Quantitative Nucleic Acid Test (NAT / Viral Load):
  • If HIV-1 RNA is detectable -> Confirms Acute HIV-1 Infection.
  • If HIV-1 RNA is undetectable -> False-positive initial screen.

Comprehensive Baseline Laboratory Evaluation

1. CD4+ T-Lymphocyte Count and Percentage: Assesses degree of immune deficiency and guides opportunistic infection prophylaxis.
2. Plasma HIV-1 RNA Viral Load: Establishes baseline virologic burden to monitor response to ART.
3. HIV Genotypic Resistance Testing: Evaluates reverse transcriptase (RT) and protease (PR) genes; obtain integrase strand transfer inhibitor (INSTI) genotype if INSTI-based therapy planned.
4. HLA-B*5701 Allele Screening: Mandatory prior to initiating Abacavir (ABC). Patients positive for HLA-B*5701 are at high risk for a fatal, multisystem Abacavir Hypersensitivity Reaction (fever, rash, GI symptoms, dyspnea). If positive, Abacavir is permanently contraindicated and must be recorded as an allergy.
5. Hepatitis Serologies: Hepatitis B (HBsAg, anti-HBs, anti-HBc) and Hepatitis C (HCV Ab with reflex RNA). Tenofovir (TDF or TAF) + Emtricitabine or Lamivudine treat both HIV and HBV.
6. G6PD Level: Baseline screening required before prescribing oxidant medications (Dapsone, Primaquine) for opportunistic infection prophylaxis/treatment.
7. STI & Latent TB Screening: Syphilis serology (RPR/VDRL), urine/mucosal NAAT for N. gonorrhoeae and C. trachomatis, and IGRA or TST for latent tuberculosis.

2. Antiretroviral Therapy (ART) & Prevention Strategies

Core Principles of ART

• Universal Indication: ART is recommended for all individuals with HIV infection, regardless of CD4 cell count, to decrease morbidity/mortality and prevent transmission (Undetectable = Untransmittable [U=U]).
• Rapid Initiation: ART should be initiated immediately (or same day as diagnosis) whenever possible.

Preferred Initial ART Regimens (2 NRTIs + 1 INSTI Backbone)

1. Bictegravir / Tenofovir Alafenamide / Emtricitabine (Biktarvy - BIC/TAF/FTC): Single-tablet regimen once daily. High barrier to resistance, excellent tolerability, no HLA-B*5701 testing required.
2. Dolutegravir / Tenofovir Alafenamide (or TDF) / Emtricitabine (or Lamivudine): (DTG + TAF/FTC or DTG + TDF/FTC).
3. Dolutegravir / Abacavir / Lamivudine (Triumeq - DTG/ABC/3TC): Single-tablet regimen; requires confirmed negative HLA-B*5701 and negative HBV status (Abacavir does not have activity against HBV).
4. Two-Drug Initial Regimen — Dolutegravir / Lamivudine (Dovato - DTG/3TC): Approved for initial therapy ONLY IF baseline HIV-1 RNA viral load is <500,000 copies/mL, patient has no Hepatitis B co-infection, and resistance testing shows no NRTI or INSTI mutations.

NRTI Comparison: TDF versus TAF

• Tenofovir Disoproxil Fumarate (TDF): Higher circulating plasma levels; associated with tubular nephrotoxicity (Fanconi syndrome, proteinuria, acute tubular injury) and loss of bone mineral density (osteopenia/osteoporosis).
• Tenofovir Alafenamide (TAF): Targeted intracellular uptake in lymphoid tissue with 90% lower plasma levels; significantly reduces renal and bone toxicities (preferred in patients with underlying renal dysfunction or osteoporosis).

Pre-Exposure Prophylaxis (PrEP) & Post-Exposure Prophylaxis (PEP)

• PrEP Regimens:
  • Daily Oral Emtricitabine / Tenofovir Disoproxil Fumarate (FTC/TDF - Truvada): Approved for all populations at risk (men who have sex with men [MSM], heterosexual men and women, injection drug users).
  • Daily Oral Emtricitabine / Tenofovir Alafenamide (FTC/TAF - Descovy): Approved for MSM and transgender women; NOT approved for individuals at risk from receptive vaginal sex (due to lack of clinical efficacy trial data in cisgender women).
  • Injectable Cabotegravir (Apretude): Extended-release IM injection administered every 2 months (following two monthly initial doses). Superior efficacy over daily oral PrEP in clinical trials.
  • Mandatory PrEP Rules: Document a negative HIV-1 Ag/Ab test and viral load within 1 week prior to initiating or renewing PrEP to prevent emerging resistance if infected. Check eGFR (>=60 for TDF; >=30 for TAF) and STI screen every 6 months.
• PEP (Post-Exposure Prophylaxis):
  • Initiated following occupational (needlestick) or non-occupational (unprotected sexual assault or intercourse) exposure.
  • Timing: Must be initiated within <=72 hours of exposure.
  • Duration & Regimen: 28-day course of 3-drug therapy: Tenofovir (TDF or TAF) + Emtricitabine (FTC) PLUS Dolutegravir (50 mg daily) OR Raltegravir (400 mg BID).